tbuckley/cabot-search huggingface dataset:
Spatiotemporally Responsive Hydrogel Dressing with Self‐Adaptive Antibacterial Activity and Cell Compatibility for Wound Sealing and Healing
Authors: Wei Zhong, Rongjian Hu, Shuai Zhou, Jianhua Xu, Kaiyuan Wang, Bowen Yao, Ranhua Xiong, Jiajun Fu
Journal: Advanced Healthcare Materials (2023)

Abstract Adhesive hydrogels containing quaternary ammonium salt (QAS) moieties have shown attractive advantages in treatment for acute wounds, attributed to their high performances in wound sealing and sterilization. However, the introduction of QAS commonly leads to high cytotoxicity and adhesive deterioration. Herein, aimed to solve these two issues, a self‐adaptive dressing with delicate spatiotemporal responsiveness is developed by employing cellulose sulfate (CS) as dynamic layers to coat QAS‐based hydrogel. In detail, due to the acid environment of wound in the early stages of healing, the CS coating will quickly detach to expose the active QAS groups for maximum disinfectant efficacy; meanwhile, as the wound gradually heals and recovers to a neutral pH, the CS will remain stable to keep QAS screened, realizing a high cell growth‐promoting activity for epithelium regeneration. Additionally, attributed to the synergy of temporary hydrophobicity by CS and slow water absorption kinetics of the hydrogel, the resultant dressing possesses outstanding wound sealing and hemostasis performance. At last, this work anticipates this approach to intelligent wound dressings based on dynamic and responsive intermolecular interaction can also be applied to a wide range of self‐adaptive biomedical materials employing different chemistries for applications in medical therapy and health monitoring.
Electronic screening for mental illness in patients with psoriasis
Authors: Katie Bechman, Joseph F Hayes, Julian  Mathewman, Alasdair D Henderson, Elizabeth I Adesanya, Kathryn E Mansfield, Catherine H Smith, James Galloway, Sinéad M Langan
Journal: British Journal of Dermatology (2023)

In this cross-sectional study from a large UK centre, screening for mental illness in individuals with psoriasis has demonstrated a high burden of depression and anxiety. Overall, 85% of the cohort reported that their psoriasis had affected their quality of life. Quality-of-life scores correlate with depression scores, emphasizing the importance of managing the individual’s mental health alongside their psoriasis to improve overall quality of life.
Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia
Authors: Floor L.F. van Baarle, Emma K. van de Weerdt, Walter J.F.M. van der Velden, Roelof A. Ruiterkamp, Pieter R. Tuinman, Paula F. Ypma, Walter M. van den Bergh, Astrid M.P. Demandt, Emile D. Kerver, A.J. Gerard Jansen, Peter E. Westerweel, Sesmu M. Arbous, Rogier M. Determann, Walther N.K.A. van Mook, Mirelle Koeman, Anja B.U. Mäkelburg, Krijn P. van Lienden, Jan M. Binnekade, Bart J. Biemond, Alexander P.J. Vlaar
Journal: New England Journal of Medicine (2023)

Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. Download a PDF of the Research Summary. In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.) QUICK TAKE VIDEO SUMMARYProphylactic Platelet Transfusion before CVC Placement 02:20
“A healthcare assistant abused my daughter while she was in a mental health facility”
Authors: Adele Waters, Ingrid Torjesen
Journal: BMJ (2023)

A healthcare assistant abused my daughter while she was in a mental health facility" Kate shares her story as part of The BMJ and Guardian's investigation into sexual assault in the NHS Adele Waters, Ingrid Torjesen Kate remembers the moment her daughter Emily (names changed), 21, told her that she had been sexually abused by a healthcare assistant in the mental health facility where she had been receiving treatment."I remember getting the phone call from her saying what had happened," says Kate. "She didn't say, 'I've been abused.'She said, 'I've been having a relationship with a member of staff.'I was really shocked, and my first thought was, 'Well, that's wrong.'"Emily was diagnosed with emotionally unstable personality disorder, a condition in which people experience intense and fluctuating emotions, at the age of 17.She had received years of treatment in mental health facilities after experiencing self-harm, suicidal thoughts, eating problems, and difficulties with interpersonal relationships.Her mother says that she attributed many of these issues to sexual abuse that Emily experienced as a child.
A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses
Authors: Kristen W. Cohen, Stephen C. De Rosa, William J. Fulp, Allan C. deCamp, Andrew Fiore-Gartland, Celia R. Mahoney, Sarah Furth, Josh Donahue, Rachael E. Whaley, Lamar Ballweber-Fleming, Aaron Seese, Katharine Schwedhelm, Daniel Geraghty, Greg Finak, Sergey Menis, David J. Leggat, Farhad Rahaman, Angela Lombardo, Bhavesh R. Borate, Vincent Philiponis, Janine Maenza, David Diemert, Orpheus Kolokythas, Nadia Khati, Jeffrey Bethony, Ollivier Hyrien, Dagna S. Laufer, Richard A. Koup, Adrian B. McDermott, William R. Schief, M. Juliana McElrath
Journal: Science Translational Medicine (2023)

The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need to be matured, through additional heterologous immunizations, into B cells that are able to produce broadly neutralizing antibodies. CD4 T cell help will be critical for the development of such high-affinity neutralizing antibody responses. Thus, we assessed the induction and epitope specificities of the vaccine-specific T cells from the IAVI G001 phase 1 clinical trial that tested immunization with eOD-GT8 60-mer adjuvanted with AS01 B . Robust polyfunctional CD4 T cells specific for eOD-GT8 and the lumazine synthase (LumSyn) component of eOD-GT8 60-mer were induced after two vaccinations with either the 20- or 100-microgram dose. Antigen-specific CD4 T helper responses to eOD-GT8 and LumSyn were observed in 84 and 93% of vaccine recipients, respectively. CD4 helper T cell epitope “hotspots” preferentially targeted across participants were identified within both the eOD-GT8 and LumSyn proteins. CD4 T cell responses specific to one of these three LumSyn epitope hotspots were observed in 85% of vaccine recipients. Last, we found that induction of vaccine-specific peripheral CD4 T cells correlated with expansion of eOD-GT8–specific memory B cells. Our findings demonstrate strong human CD4 T cell responses to an HIV vaccine candidate priming immunogen and identify immunodominant CD4 T cell epitopes that might improve human immune responses either to heterologous boost immunogens after this prime vaccination or to other human vaccine immunogens.
Issue 2 - “Update on adverse respiratory effects of indoor air pollution” Part 1): Indoor air pollution and respiratory diseases: A general update and a Portuguese perspective
Authors: J.C. Rufo, I. Annesi-Maesano, P. Carreiro-Martins, A. Moreira, A.C. Sousa, M.R. Pastorinho, N. Neuparth, L. Taborda-Barata
Journal: Pulmonology (2023)

To quantify the impact of different air pollutants on respiratory health based on robust estimates based on international data and to summarise the evidence of associations between indoor exposure to those pollutants and respiratory morbidity in the Portuguese population. Several systematic reviews and meta-analyses (MA) at the world level demonstrate the impact of indoor air quality on respiratory health, with indoor particulate matter and gasses exerting a significant effect on the airways. Volatile organic compounds (VOC) have been related to asthma and lung cancer. However, only meta-analyses on biomass use allowed documentation of long-term respiratory effects. While early publications concerning Portuguese-based populations mainly focused on indoor exposure to environmental tobacco smoke, later studies relocated the attention to relevant exposure environments, such as day care buildings, schools, residences and nursing homes. Looking at the pooled effects from the reviewed studies, high levels of carbon dioxide and particulate matter in Portuguese buildings were significantly associated with asthma and wheezing, with VOC and fungi showing a similar effect in some instances. Despite the significant reduction of indoor air pollution effects after the 2008 indoor smoking prohibition in public buildings, studies show that several indoor air parameters are still significantly associated with respiratory health in Portugal. The country shares the worldwide necessity of standardisation of methods and contextual data to increase the reach of epidemiological studies on household air pollution, allowing a weighted evaluation of interventions and policies focused on reducing the associated respiratory morbidity.
Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial
Authors: Thomas John, Christian Grohé, Jonathan W. Goldman, Frances A. Shepherd, Filippo de Marinis, Terufumi Kato, Qun Wang, Wu-Chou Su, Jin Hyuk Choi, Virote Sriuranpong, Barbara Melotti, Mary J. Fidler, Jun Chen, Muna Albayaty, Marta Stachowiak, Sarah Taggart, Yi-Long Wu, Masahiro Tsuboi, Roy S. Herbst, Margarita Majem
Journal: Journal of Thoracic Oncology (2023)

In ADAURA, adjuvant osimertinib significantly improved disease-free survival versus placebo in resected stage IB to IIIA EGFR-mutated NSCLC. We report in-depth analyses of three-year safety, tolerability, and health-related quality of life (HRQoL) from ADAURA.Patients were randomized 1:1 to osimertinib 80 mg or placebo once daily for up to 3 years. Safety assessments were performed at baseline, week 2, week 4, week 12, and every 12 weeks until treatment completion or discontinuation, and 28 days after treatment was stopped. The SF-36 survey measured HRQoL at baseline, week 12, week 24, and every 24 weeks until recurrence, treatment completion or discontinuation. Data cutoff: April 11, 2022.Safety and HRQoL analysis sets: osimertinib, n = 337 and n = 339; placebo, n = 343 each. Median (range) total exposure duration was longer with osimertinib versus placebo: 35.8 (0-38) versus 25.1 (0-39) months. Most adverse events (AEs) were first reported within 12 months of starting treatment (osimertinib 97%, placebo 86%). AEs leading to dose reduction, interruption or discontinuation were reported in 12%, 27% and 13% respectively of patients with osimertinib; 1%, 13% and 3% with placebo. Stomatitis and diarrhea were the most common AEs leading to osimertinib dose reduction or interruption; interstitial lung disease was the most common leading to osimertinib discontinuation (per protocol). There were no differences in time to deterioration for SF-36 physical, mental component summaries between osimertinib and placebo.No new safety signals were reported and HRQoL was maintained with 3 years of adjuvant osimertinib treatment. Combined with significant efficacy benefit, these data further support adjuvant osimertinib in stage IB to IIIA EGFR-mutated NSCLC.
New opportunities for RGD-engineered metal nanoparticles in cancer
Authors: Wei Qin, Jyoti Chandra, Mohammed A.S. Abourehab, Neelima Gupta, Zhe-Sheng Chen, Prashant Kesharwani, Hui-Ling Cao
Journal: Molecular Cancer (2023)

The advent of nanotechnology has opened new possibilities for bioimaging. Metal nanoparticles (such as gold, silver, iron, copper, etc.) hold tremendous potential and offer enormous opportunities for imaging and diagnostics due to their broad optical characteristics, ease of manufacturing technique, and simple surface modification. The arginine-glycine-aspartate (RGD) peptide is a three-amino acid sequence that seems to have a considerably greater ability to adhere to integrin adhesion molecules that exclusively express on tumour cells. RGD peptides act as the efficient tailoring ligand with a variety of benefits including non-toxicity, greater precision, rapid clearance, etc. This review focuses on the possibility of non-invasive cancer imaging using metal nanoparticles with RGD assistance.
Comprehensive genomic profiling and treatment patterns across ancestries in advanced prostate cancer: a large-scale retrospective analysis
Authors: Smruthy Sivakumar, Jessica K Lee, Jay A Moore, Julia Hopkins, Justin Y Newberg, Russell Madison, Ryon Graf, Alexa B Schrock, Erin Kobetz, Randy Vince, Idalid Franco, Crystal Seldon, Garrett M Frampton, Jennifer Mills, Jeffrey Venstrom, Brandon A Mahal
Journal: The Lancet Digital Health (2023)

Men of African ancestry experience the greatest burden of prostate cancer globally, but they are under-represented in genomic and precision medicine studies. Therefore, we sought to characterise the genomic landscape, comprehensive genomic profiling (CGP) utilisation patterns, and treatment patterns across ancestries in a large, diverse, advanced prostate cancer cohort, to determine the impact of genomics on ancestral disparities.In this large-scale retrospective analysis, the CGP-based genomic landscape was evaluated in biopsy sections from 11 741 patients with prostate cancer, with ancestry inferred using a single nucleotide polymorphism-based approach. Admixture-derived ancestry fractions for each patient were also interrogated. Independently, clinical and treatment information was retrospectively reviewed for 1234 patients in a de-identified US-based clinicogenomic database. Prevalence of gene alterations, including actionable gene alterations, was assessed across ancestries (n=11 741). Furthermore, real-world treatment patterns and overall survival was assessed in the subset of patients with linked clincogenomic information (n=1234).The CGP cohort included 1422 (12%) men of African ancestry and 9244 (79%) men of European ancestry; the clinicogenomic database cohort included 130 (11%) men of African ancestry and 1017 (82%) men of European ancestry. Men of African ancestry received more lines of therapy before CGP than men of European ancestry (median of two lines [IQR 0-8] vs one line [0-10], p=0·029). In genomic analyses, ancestry-specific mutational landscapes were observed, but the prevalence of alterations in AR, the DNA damage response pathway, and other actionable genes were similar across ancestries. Similar genomic landscapes were observed in analyses that accounted for admixture-derived ancestry fractions. After undergoing CGP, men of African ancestry were less likely to receive a clinical study drug compared with men of European ancestry (12 [10%] of 118 vs 246 [26%] of 938, p=0·0005).Similar rates of gene alterations with therapy implications suggest that differences in actionable genes (including AR and DNA damage response pathway genes) might not be a main driver of disparities across ancestries in advanced prostate cancer. Later CGP utilisation and a lower rate of clinical trial enrolment observed in men of African ancestry could affect genomics, outcomes, and disparities.American Society for Radiation Oncology, Department of Defense, Flatiron Health, Foundation Medicine, Prostate Cancer Foundation, and Sylvester Comprehensive Cancer Center.
Wearable devices: underrepresentation in the ageing society
Authors: Ta-Wei Guu, Marijn Muurling, Zunera Khan, Chris Kalafatis, Dag Aarsland, Dominic ffytche, Anna-Katharine Brem
Journal: The Lancet Digital Health (2023)

In The Lancet Digital Health, Zinzuwadia and Singh commented on the bias and inequity in studies that make use of wearable devices among the general population.1 We appreciate their efforts to widen the known issue of insufficient representation from racially minoritised people, to people from low-income or rural communities, and other populations with poorer access to digital literacy. However, they did not properly address older populations, especially those who are most likely to benefit from remote monitoring and wearable device technology—people living with age-related cognitive decline and dementia.
Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease
Authors: Edward V. Loftus, Julian Panés, Ana P. Lacerda, Laurent Peyrin-Biroulet, Geert D’Haens, Remo Panaccione, Walter Reinisch, Edouard Louis, Minhu Chen, Hiroshi Nakase, Jakob Begun, Brigid S. Boland, Charles Phillips, Mohamed-Eslam F. Mohamed, Jianzhong Liu, Ziqian Geng, Tian Feng, Elena Dubcenco, Jean-Frederic Colombel
Journal: New England Journal of Medicine (2023)

Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. Download a PDF of the Research Summary. In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]). A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib. Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. (Funded by AbbVie; U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.) QUICK TAKE VIDEO SUMMARYUpadacitinib for Crohn's Disease 02:52
“He’s left me feeling vulnerable, and I’m so angry”
Authors: Adele Waters, Ingrid Torjesen
Journal: BMJ (2023)

Megan (name changed) was assaulted by Wayne Bronze, who was later struck off by the Nursing and Midwifery Council, in 2016. She shares her story as part of <i>The BMJ </i>and <i>Guardian</i>’s investigation into sexual assault in the NHS
Meningococcal ACWYX Conjugate Vaccine in 2-to-29-Year-Olds in Mali and Gambia
Authors: Fadima C. Haidara, Ama Umesi, Samba O. Sow, Magnus Ochoge, Fatoumata Diallo, Abdulazeez Imam, Youssouf Traore, Lucy Affleck, Moussa F. Doumbia, Bubacarr Daffeh, Mamoudou Kodio, Oghenebrume Wariri, Awa Traoré, Edrissa Jallow, Beate Kampmann, Dhananjay Kapse, Prasad S. Kulkarni, Asha Mallya, Sunil Goel, Pankaj Sharma, Annamraju D. Sarma, Nikhil Avalaskar, F. Marc LaForce, Mark R. Alderson, Abdi Naficy, Steve Lamola, Yuxiao Tang, Lionel Martellet, Nancy Hosken, Evangelos Simeonidis, Jo Anne Welsch, Milagritos D. Tapia, Ed Clarke
Journal: New England Journal of Medicine (2023)

An effective, affordable, multivalent meningococcal conjugate vaccine is needed to prevent epidemic meningitis in the African meningitis belt. Data on the safety and immunogenicity of NmCV-5, a pentavalent vaccine targeting the A, C, W, Y, and X serogroups, have been limited.
Antibody-Drug Conjugates in Lung Cancer: Recent Advances and Implementing Strategies
Authors: Antonio Passaro, Pasi A. Jänne, Solange Peters
Journal: Journal of Clinical Oncology (2023)

Antibody-drug conjugates (ADCs) are one of the fastest-growing oncology therapeutics, merging the cytotoxic effect of conjugated payload with the high specific ability and selectivity of monoclonal antibody targeted on a specific cancer cell membrane antigen. The main targets for ADC development are antigens commonly expressed by lung cancer cells, but not in normal tissues. They include human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, trophoblast cell surface antigen 2, c-MET, carcinoembryonic antigen-related cell adhesion molecule 5, and B7-H3, each with one or more specific ADCs that showed encouraging results in the lung cancer field, more in non-small-cell lung cancer than in small-cell lung cancer histology. To date, multiple ADCs are under evaluation, alone or in combination with different molecules (eg, chemotherapy agents or immune checkpoint inhibitors), and the optimal strategy for selecting patients who may benefit from the treatment is evolving, including an improvement of biomarker understanding, involving markers of resistance or response to the payload, besides the antibody target. In this review, we discuss the available evidence and future perspectives on ADCs for lung cancer treatment, including a comprehensive discussion on structure-based drug design, mechanism of action, and resistance concepts. Data were summarized by specific target antigen, biology, efficacy, and safety, differing among ADCs according to the ADC payload and their pharmacokinetics and pharmacodynamics properties.